Mucopolysaccharidosis type 2, attenuated form

Mucopolysaccharidosis type 2, attenuated form (also known as attenuated Hunter syndrome or MPS II, attenuated type) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase (IDS), which is needed to break down the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate. The accumulation of these GAGs in cells and tissues throughout the body leads to progressive multi-organ damage. The attenuated form is distinguished from the severe form by the absence of significant central nervous system involvement and a slower disease progression, with patients typically surviving into adulthood. The attenuated form of MPS II affects multiple body systems. Key clinical features include joint stiffness and contractures, coarse facial features, short stature, skeletal abnormalities (dysostosis multiplex), hepatosplenomegaly (enlarged liver and spleen), cardiac valve disease, hearing loss, and upper airway obstruction. Carpal tunnel syndrome is common. Corneal clouding, which is characteristic of some other MPS types, is generally absent in MPS II. Cognitive function is typically preserved or only mildly affected in the attenuated form, though some patients may experience mild learning difficulties. Symptoms usually become apparent in childhood but progress more slowly than in the severe form. Treatment options include enzyme replacement therapy (ERT) with idursulfase (Elapreva/Elaprase), which has been approved and shown to improve walking capacity, reduce organ size, and improve respiratory function. ERT does not cross the blood-brain barrier effectively, but this is less of a concern in the attenuated form where neurological involvement is minimal. Hematopoietic stem cell transplantation (HSCT) has been explored but is not standard treatment for MPS II. Supportive care including physical therapy, surgical interventions for airway management, cardiac monitoring, and hearing aids are important components of management. Clinical trials investigating intrathecal ERT and gene therapy are ongoing.

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